Several publications and patent documents are referenced in this application in order to more fully describe the state of the art to which this invention pertains. The disclosure of each of these publications and documents is incorporated by reference herein.
Traumatic brain injury (TBI) is one of the leading causes of death and disabilities among all traumas and an increasing body of literature implicates TBI as an independent risk factor for developing Alzheimer's disease (AD).1-9 The incidence of TBI in the US is comparable to stroke, but affects younger people resulting in a greater health care burden.10 
TBI covers a wide range of injuries, from mild to moderate and severe. Factors that influence the neuropathology such as the number of repeated impacts, types and extent of injury, and regions of the brain where the trauma occurs have not yet been clearly elucidated. In spite of the fact that most cases of TBI are mild or moderate, most of the TBI animal model systems and studies have focused on severe TBI (sTBI). Even so, reliable predictors of sTBI outcome, particularly during the early stages following neurotrauma, have not been established and are being sought. This emphasizes the need to identify and characterize reliable neurological and biochemical TBI biomarkers for diagnosis and prognosis. Currently, a TBI patient is evaluated only by clinical assessment and neuroimaging, which have their own limitations in predicting the functional impairments associated with the chronic conditions that accompany a significant TBI. Historically, classification of TBI severity has been based on a Glascow Coma Scale (GCS) score, but this widely used clinical neurological score may be influenced by unrelated factors such a patients consumption of drugs or alcohol, prescribed medications and other extracerebral injuries. Therefore, establishing a complementary approach of patient evaluation using neurological assessment in combination with biochemical biomarkers will reliably and objectively determine the severity of a TBI which can then guide treatment regimens.11-20 
Tau is a microtubule-associated protein localized mainly in neuronal cells and functions as a major structural element in the axonal cytoskeleton. Total tau (T-tau) is abundant in the CNS, and in particular, in unmyelinated axons and cortical interneurons.21, 22 Under normal circumstances, the phosphorylation of tau (P-tau) is responsible for regulating its biological activity. However, excessive tau phosphorylation (i.e. hyperphosphorylation) is associated with several neurodegenerative diseases and are referred to as tauopathies.23-25 For example, one of the hallmarks of AD is the presence of neurofibrillary tangles (NFTs) that are composed of P-tau that forms paired helical filaments (PHFs), and also includes increased T-tau and P-tau in the CSF.22, 26, 27 Pathological phosphorylation of tau has been found at a number of sites including Thr-181, Ser-198, Ser-199, Ser-202, Thr-205, Thr-231, Ser-356, Ser-404 and Ser-422, which are phosphorylated by casein kinases, cyclic AMP-dependent protein kinase, glycogen synthase kinase-3β (GSK-3β), cyclic AMP-dependent protein kinase, cyclin-dependent kinase 5 and tau-tubulin kinases (TTBK).28-32 
The analysis of P-tau is crucial in the diagnosis of AD.33 However, the significance of P-tau levels following TBI is unclear. Rodent TBI models do not produce NFTs post-injury. However, tau-associated neuropathology, mainly being the presence of NFTs, has been reported in the brains of athletes who have played contact sports (boxers, football and ice hockey players, wrestlers) and who sustained concussions during their career. This pathological condition has been termed Chronic Traumatic Encephalopathy (CTE).37-42 Common symptoms in CTE include memory loss, Parkinson-like movements, dementia, aggression, confusion and depression.38, 41, 43-46 Although the majority of CTE cases display widespread NFTs, in contrast to AD, Aβ pathology is less frequent.42, 47 
Reports on the time course of T-tau and P-tau levels following TBI are limited and include Gabbita et al.48 and Liliang et al.49. We previously described the development of an assay termed SOFIA (Surround Optical Fiber Immunoassay) for the detection of the abnormal prion protein in prion diseased animals and humans.50-54 As a result of our continued efforts to develop advanced biomarker assay technologies from readily accessible samples, we have changed the term SOFIA to EIMAF (Enhanced Immunoassay using Multi-Arrayed Fiberoptics).
Increased tau levels have been reported in the CSF following TBI and also show promise as a specific serum biomarker in both human patients and experimental models.13, 15, 16, 34-36 Although there is a rapid rise in tau protein levels in the CSF post-TBI,13, 34 the peak and temporal progression of serum tau levels have not been adequately evaluated.15, 16 It is an object of the invention to provide an ultrasensitive assay to facilitate this evaluation.